Current hypotheses on the escape of tumors from normal growth controls center on the production of growth stimulating and inhibiting factors by tumor cells. We have examined this hypothesis by assessing growth factor production by normal and neoplastic human mammary cells in culture and in freshly isolated tissues. Four growth factors have been purified from these sources, including MDGFI, MDGFII, transforming growth factor alpha (TGFAlpha), and transforming growth factorBeta (TGFBeta). MDGFI has been purified to apparent homogeneity. It is a Mr 62,000 acidic protein that binds to specific, high affinity receptors on mammary cells. Factors that compete with MDGFI for receptor binding were detected in conditioned medium from primary cultures of mammary epithelium from normal and malignant tissues. Based on these assays, the production of MDGFI was estimated to be two to three times higher in malignant than normal breast cells. MDGFII was purified about 10,000 fold from human milk. The factor has an apparent molecular weight of 17,000 and pI of 4.0. It competes with EGF and TGFAlpha for receptor binding but differs from the latter two factors in size and pI. Using a soft agar cloning assay, both normal and neoplastic mammary cells were found to produce large and roughly equivalent amounts of TGFBeta. TGFAlpha mRNA levels were found to correlate positively with estrogen and progesterone receptor levels in human and rodent mammary tumors. In rodents, a dramatic fall in mRNA levels were seen within three hours of ovariectomy, suggesting ovarian steroids regulate TGFAlpha production. Both human and rodent mammary tumors contain an inhibitor of mammary cell proliferation. The factor has been partially purified and found to be a Mr 13,000 protein with a pI of 5.0. It cross reacts with antisera against a similar factor made by bovine mammary glands. These results suggest that cell growth control is effected by positive and negative growth regulatory substances made by tumors.